Hepatitis C Drug Pipeline

Category Archives: AbbVie

AASLD 2016 Conference: AbbVie

Phase 3 Clinical Trials:

Four studies of AbbVie’s two drug combination—glecaprevir (protease inhibitor) and pibrentasvir (NS5A inhibitor) were presented.

Endurance 1:703 genotype 1 non-cirrhotic treatment naïve and treatment experience patients. The patients were treated for 8 or 12 weeks. No ribavirin was used in the study. The cure rates were 99% to 100% across all treatment groups. Endurance 2: 199 genotype 2 non-cirrhotic treatment-naïve and treatment-experience patients treated for 12 weeks achieved 99% to 100%.

Surveyor-II Part 3 Phase 2/3: In genotype 3 patients who were cirrhotic and treatment experienced but who had not been previously treated with a NS5A inhibitor were treated with glecaprevir plus pibrentasvir. Those treated for 12 weeks achieved 91% to 98% cure rates and those treated for 16 weeks achieved 96% cure rates. This treatment was particularly effective for people with end-stage kidney disease.

Surveyor-II Part 4: In genotype 2, 4, 5 or 6 patients without cirrhosis. There were a total of 203 patients—both treatment naïve and treatment experienced (no NS5A treatment experienced). The treatment period was 8 weeks. The cure rates were 98% for genotype 2; 93% for genotype 4; 100% for genotype 5 and 90% for genotype 6—although the number of patients in the genotype 5 and 6 groups were very small.

Expedition-IV: The goal of the study was to treat patients with renal impairment. There were 104 genotype 1 through 6 patients enrolled. The majority of the patients had severe renal impairment, and 82% were on dialysis (filtering of the blood because the kidneys are impaired). The patients were treatment naïve and treatment experienced (no NS5A experienced). The cure rate was 99% (103 of 104)—one patient discontinued treatment before the trial ended.

AbbVie has submitted their study results to the Food and Drug Administration forapproval inDecember.

Alan Franciscus is the Executive Director of the Hepatitis C Support Project and Editor-in-Chief of the HCV Advocate.

– Japan has one of the highest rates of hepatitis C infection in the industrialized world affecting approximately 1 million people, 60 to 70 percent of those GT1[1,2,3]– Results demonstrated in CERTAIN-1 study are consistent with recently announced 8-week, GT1 data from the global registrational studies for G/P

NORTH CHICAGO, Ill.,Jan. 9, 2017/PRNewswire/ — AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced high SVR12rates with 8 weeks of treatment with its investigational, pan-genotypic, ribavirin (RBV)-free regimen of glecaprevir (ABT-493)/pibrentasvir (ABT-530) (G/P) in Japanese patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection without cirrhosis. In top-line results from the Phase 3 CERTAIN-1 study, 99 percent (n=105/106) of patients without cirrhosis, which represents the majority of HCV patients, and without the Y93H variant achieved sustained virologic response at 12 weeks post treatment (SVR12). The only patient in whom SVR12was not documented in this intent to treat (ITT) population was lost to follow-up.All 23 patients with the Y93H variant were assigned to the G/P arm and achieved SVR12.

These data are the first to be released from registrational studies inJapanas part of AbbVie’s global G/P clinical development program, designed to investigate a faster path to virologic cure* for all major HCV genotypes and with the goal of addressing treatment areas of continued unmet need.

“These initial data in GT1-infected patients, which is the most common type of hepatitis C inJapan, may help to further advance our understanding on how we care for patients in this country,” saidStefan Zeuzem, M.D., Chief of the Department of Medicine at theGoethe UniversityHospital inFrankfurt, Germany. “In the CERTAIN-1 study with the G/P regimen, we see for the first time that 8 weeks of treatment achieved high cure rates in these GT1-infected Japanese patients without cirrhosis.”

Japanhas one of the highest rates of hepatitis C infection in the industrialized world.2Approximately 1 million people are living with hepatitis C inJapan, with 60 to 70 percent of those infected with GT1 chronic HCV.1,3Patients included in the CERTAIN-1 study were further representative of the HCV-infected patient population inJapan, where the prevalence of HCV infection increases with age, by including a majority of patients over 65 years of age.4

“Due to patient characteristics and virological considerations, people living with HCV inJapanhave specific treatment challenges and needs,” saidMichael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. “AbbVie’s dedicated G/P registrational clinical development program inJapanreflects our continued commitment to make a real difference in the lives of Japanese patients.”

The CERTAIN-1 study compared the safety and efficacy of 8 weeks of treatment with the investigational G/P regimen, to 12 weeks of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r), in GT1 chronic HCV-infected patients. The primary endpoint of the study was met, as 8 weeks of G/P was shown to be non-inferior to 12 weeks of OBV/PTV/r (100 percent SVR12; n=52).

Additionally, in substudy 1 evaluating GT1 patients (treated with G/P) without cirrhosis and who are new to treatment with direct-acting antivirals (DAA), no patients discontinued treatment due to adverse events (AEs). In patients treated with OBV/PTV/r, there was one who discontinued treatment due to AEs. In patients receiving the G/P regimen, the most common AEs, occurring at a rate greater than 5 percent, were nasopharyngitis (inflammation of the throat and nasal passages) and pruritus (itchiness).

About the CERTAIN-1 StudyThe CERTAIN-1 study is a Phase 3, multicenter study evaluating the efficacy, safety and pharmacokinetics (PK) of G/P in Japanese adults. Substudy 1 is randomized, open-label, active-controlled, in genotype 1 (GT1) chronic HCV-infected patients without cirrhosis and who are new to DAA treatment. Patients who tested negative for Y93H resistance associated variant received either 8 weeks of G/P or 12 weeks of OBV/PTV/r (2:1 randomization ratio). All Y93H positive patients were assigned to receive 8 weeks of G/P and all (n=23/23) achieved SVR12. The primary objectives were safety and non-inferiority of G/P compared to OBV/PTV/r.

Substudy 2 is a non-randomized, open-label study evaluating GT1-6 HCV patients with specific treatment challenges, including those with compensated cirrhosis (Child-Pugh A), chronic kidney disease (CKD) and those who were not cured with previous DAA treatment.

Additional data will be presented at an upcoming scientific congress.

About AbbVie’s G/P Clinical Development ProgramAbbVie’s glecaprevir/pibrentasvir (G/P) clinical development program was designed to investigate a faster path to virologic cure* for all major HCV genotypes (GT1-6) and with the goal of addressing treatment areas of continued unmet need. InJapan, AbbVie studied the G/P regimen in additional dedicated clinical trials due to patient and viral characteristics specific to the Japanese HCV patient population.

G/P is an investigational, pan-genotypic regimen that is being evaluated as a potential cure in 8 weeks for HCV patients without cirrhosis and who are new to treatment with direct-acting antivirals (DAA), who make up the majority of HCV patients. AbbVie is also studying G/P in patients with specific treatment challenges, such as genotype 3, patients who were not cured with previous DAA treatment and those with chronic kidney disease, including patients on dialysis.

G/P is an investigational, once-daily regimen that combines two distinct antiviral agents in a fixed-dose combination of glecaprevir (300mg), an NS3/4A protease inhibitor, and pibrentasvir (120mg), an NS5A inhibitor. G/P is dosed once-daily as three oral tablets.

Glecaprevir (GLE) was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors.

G/P is an investigational product and its safety and efficacy have not been established inJapan.

*Patients with a sustained virologic response at 12 weeks post treatment (SVR12) are considered cured of hepatitis C.

About VIEKIRAX inJapanVIEKIRAX (ombitasvir/paritaprevir/ritonavir) is indicated for the improvement of viremia in chronic hepatitis C or compensated hepatic cirrhosis C in patients of serogroup 1 (genotype 1) and for chronic hepatitis C in patients of serogroup 2 (genotype 2).

Positive result for HCV RNA should be confirmed before administering VIEKIRAX and decompensated cirrhosis should be excluded.

For genotype 2, since efficacy varies due to subtype and prior treatment experience with or without IFN the benefit-risk of VIEKIRAX treatment should be considered. Since VIEKIRAX is coadministered with ribavirin in genotype 2, precautions for use of the package insert of ribavirin must be confirmed.

When VIEKIRAX is used for patients co-infected with HIV/HCV, administer VIEKIRAX only to patients whose virological suppression has been achieved by anti-HIV therapy as ritonavir may cause resistance against a HIV protease inhibitor.

During the administration of VIEKIRAX, perform liver function tests regularly because hepatic function disorder may occur.

While HCV viral load is decreased, HBV reactivation in patients who are chronic infection of HBV or patients who have a history of HBV infection has been reported after initiation of HCV DAA treatment.

Renal function tests should be performed prior to an initiation and periodically after initiation of VIEKIRAX.

Co-administration of VIEKIRAX with drugs that are substrates of CYP3A4, P-gp, BCRP, OATP1B1 or OATP1B3 may result in increased plasma concentrations of such drugs, potentially requiring dose adjustment or clinical monitoring.

The safety of VIEKIRAX in pregnant women has not been established. VIEKIRAX should be used in pregnant women and women who may possibly be pregnant only if the expected therapeutic benefits outweigh the possible risks associated with treatment. VIEKIRAX in combination with ribavirin must not be used in patients who are pregnant or may be pregnant.

Do not administer VIEKIRAX to nursing mothers. If VIEKIRAX is administered to a nursing mother by necessity, breast feeding must be discontinued during treatment.

About AbbVieAbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world’s most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visitwww.abbvie.com. Follow@abbvieon Twitter or view careers on ourFacebook orLinkedInpage.

Forward-Looking StatementsSome statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words “believe,” “expect,” “anticipate,” “project” and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie’s operations is set forth in Item 1A, “Risk Factors,” of AbbVie’s 2015 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

Four studies of AbbVie’s two drug combination—glecaprevir (protease inhibitor) and pibrentasvir (NS5A inhibitor) were presented.

Endurance 1:703 genotype 1 non-cirrhotic treatment naïve and treatment experience patients. The patients were treated for 8 or 12 weeks. No ribavirin was used in the study. The cure rates were 99% to 100% across all treatment groups. Endurance 2: 199 genotype 2 non-cirrhotic treatment-naïve and treatment-experience patients treated for 12 weeks achieved 99% to 100%.

Surveyor-II Part 3 Phase 2/3: In genotype 3 patients who were cirrhotic and treatment experienced but who had not been previously treated with a NS5A inhibitor were treated with glecaprevir plus pibrentasvir. Those treated for 12 weeks achieved 91% to 98% cure rates and those treated for 16 weeks achieved 96% cure rates. This treatment was particularly effective for people with end-stage kidney disease.

Surveyor-II Part 4: In genotype 2, 4, 5 or 6 patients without cirrhosis. There were a total of 203 patients—both treatment naïve and treatment experienced (no NS5A treatment experienced). The treatment period was 8 weeks. The cure rates were 98% for genotype 2; 93% for genotype 4; 100% for genotype 5 and 90% for genotype 6—although the number of patients in the genotype 5 and 6 groups were very small.

Expedition-IV: The goal of the study was to treat patients with renal impairment. There were 104 genotype 1 through 6 patients enrolled. The majority of the patients had severe renal impairment, and 82% were on dialysis (filtering of the blood because the kidneys are impaired). The patients were treatment naïve and treatment experienced (no NS5A experienced). The cure rate was 99% (103 of 104)—one patient discontinued treatment before the trial ended.

AbbVie has submitted their study results to the Food and Drug Administration forapproval inDecember.

Alan Franciscus is the Executive Director of the Hepatitis C Support Project and Editor-in-Chief of the HCV Advocate.

“These results move us closer to our ultimate goal of providing a treatment option for as many hepatitis C patients as possible. We will continue to examine our investigational, pan-genotypic regimen through our dedicated clinical trial program, including an eight-week duration across all genotypes,” saidRob Scott, M.D., vice president, development and chief medical officer, AbbVie.

In separate late-breaking data from the SURVEYOR-2 study, 100 percent of GT3 chronic HCV infected patients with compensated cirrhosis (Child-Pugh A) new to therapy achieved SVR12with 12 weeks of treatment both with and without RBV (n=24/24 in each arm).3No patients discontinued treatment due to adverse events.3Data in GT3 chronic HCV infected patients with and without cirrhosis were featured in the official ILC 2016 press program.

“The recent evolution in hepatitis C treatment has resulted in high cure rates for many patients with specific genotypes, but there remain distinct areas of unmet need,” saidPaul Kwo, M.D., professor of medicine at theIndiana University School of Medicine. “These new data show us the potential of ABT-493 and ABT-530 in genotype 3 patients new to therapy even with the added complication of compensated cirrhosis.”

In a pooled analysis of 531 patients across both SURVEYOR studies, of five treatment regimens of ABT-493 and ABT-530 evaluated, the most commonly reported adverse events were fatigue (18 percent), headache (17 percent), nausea (13 percent) and diarrhea (10 percent).5Three patients across all study arms evaluated to date, two of whom received RBV, discontinued study drugs early due to adverse events.5

Overview of SURVEYOR-1 and SURVEYOR-2 Clinical Data Presented at ILC:

Patient Profile/Study

Patient number (n)/

Patient Population

Duration of Treatment

Treatment Regimen

SVR12Rates

ITT*

GT1

Non-cirrhotic1

SURVEYOR-1

n=34

Treatment-naïve=85%

pegIFN/RBV treatment experienced=15%

8 weeks

ABT-493 (300mg) + ABT-530 (120mg) once daily

97%

(n=33/34)

GT2

Non-cirrhotic1

SURVEYOR-2

n=54

Treatment-naïve=87%

pegIFN/RBV treatment

experienced=13%

8 weeks

ABT-493 (300mg) + ABT-530 (120mg) once daily

98%

(n=53/54)

GT3

Non-cirrhotic2

SURVEYOR-2

n=29

Treatment-naïve =100%

8 weeks

ABT-493 (300mg) + ABT-530 (120mg) once daily

97%

(n=28/29)

GT3

Cirrhotic3

(Child-Pugh A)

SURVEYOR-2

n=24

Treatment-naïve= 100%

12 weeks

ABT-493 (300mg) + ABT-530 (120mg) without RBV

once daily

100%

(n=24/24)

n=24

Treatment-naïve=100%

12 weeks

ABT-493 (300mg) + ABT-530 (120mg) +

RBV (800mg)

once daily

100%

(n=24/24)

GT 4,5,6

Non-cirrhotic4

SURVEYOR-1

n=34

(GT4=22; GT5=1; GT6=11)

Treatment-naïve=85%

pegIFN/RBV treatment experienced=15%

12 weeks

ABT-493 (300mg) + ABT-530 (120mg) once daily

100%

(n=34/34)

*

Intent-to-treat (ITT) population is defined as all patients who received at least one dose of the study drugs

About SURVEYOR-11,4,5SURVEYOR-1 is an ongoing Phase 2 two-part study designed to evaluate the safety and efficacy of ABT-493 and ABT-530, with and without RBV, for eight to 12 weeks, in cirrhotic and non-cirrhotic adult genotype 1 patients, and non-cirrhotic adult patients with genotypes 4, 5 or 6 chronic HCV infection who were new to therapy or did not respond to previous treatment with pegylated interferon (pegIFN)/RBV (null responder).

About SURVEYOR-21,2,3,5SURVEYOR-2 is an ongoing Phase 2, four-part study designed to evaluate the safety and efficacy of ABT-493 and ABT-530, with or without RBV, in adult patients with genotypes 2, 3, 4, 5 or 6 chronic HCV infection who were new to therapy or had failed previous treatment with pegylated interferon (pegIFN)/RBV.

The primary endpoint of both studies is the percentage of subjects achieving SVR12.

Safety and efficacy data for Part 1 of the studies were presented at The Liver Meeting® 2015, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) inSan Francisco.

About pooled safety analysis of SURVEYOR-1 and SURVEYOR-25531 patients were included in this safety analysis: 26 percent GT1, 24 percent GT2, 43 percent GT3, and 6 percent with GT4, 5 or 6 infection. Patients across genotypes received ABT-493/ABT-530 at five doses: 300/120mg (n=258), 300/120mg with RBV (n=27), 200/120mg (n=121), 200/120mg with RBV (n=56), and 200/40mg (n=69).

About AbbVie’s HCV Clinical Development ProgramAbbVie’s HCV clinical development program is intended to advance scientific knowledge and the clinical care of people with chronic HCV infection by investigating pan-genotypic (genotypes 1-6), all-oral, ribavirin-free, once-daily treatment for 12 weeks. An eight-week treatment duration with ABT-493 and ABT-530 will be investigated across all genotypes in our comprehensive Phase 2/Phase 3 clinical trial program, which focuses on areas of ongoing need in HCV.

ABT-493 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors.

About AbbVieAbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world’s most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visitwww.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

1Poordad, F et al. High SVR Rates with the Combination of ABT-493 + ABT-530 for 8 Weeks in Non-Cirrhotic Patients with HCV Genotype 1 or 2 Infection. Poster presentation #SAT-157; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) inBarcelona, Spain,April 13-17, 2016.2Muir, A et al. High SVR Rates with ABT-493 + ABT-530 Co-Administered for 8 Weeks in Non-Cirrhotic Patients with HCV Genotype 3 Infection. Oral presentation #PS098; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) inBarcelona, Spain,April 13-17, 2016.3Kwo, P et al. 100% SVR12with ABT-493 And ABT-530 with or without Ribavirin in Treatment-Naïve HCV Genotype 3-Infected Patients with Cirrhosis; Late Breaker presentation #LB01; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) inBarcelona, Spain,April 13-17, 20164 Gane, E et al. 100% SVR4and Favorable Safety of ABT-493 + ABT-530 Administered for 12 Weeks in Non-Cirrhotic Patients with Genotypes 4,5, or 6 Infection (SURVEYOR-I). Poster presentation #SAT-137; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) inBarcelona, Spain,April 13-17, 2016.5Kwo, P et al. Safety of ABT-493 and ABT-530 Co-Administered in Patients with HCV Genotype 1-6 Infection: Results From the SURVEYOR-I and SURVEYOR-II Studies; Poster presentation #SAT-239; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) inBarcelona, Spain,April 13-17, 2016.

On January 7, 2015, AbbVie issued a press release that the FDA had granted Viekira Pak without ribavirin a priority review status for the treatment of hepatitis C genotype 1b in people with compensated cirrhosis. AbbVie did not provide details on an expected FDA approval date.

AbbVie submitted data to the FDA based on the Phase IIIb TURQUOISE-III study of 60 genotype 1b patients treated with Viekira Pak (ombitasvir, paritaprevir/ritonavir, dasabuvir) for a treatment duration of 12 weeks. The cure rates were 100% (60 of 60 pts). The most common side effects were fatigue, diarrhea, headache and joint pain.

ABT-493 (protease inhibitor) plus ABT-530 (NS5A inhibitor) co-formulated into one pill, taken once-a-day is currently in phase 3 clinical trials to treat genotypes 1 through 6. The treatment duration for most of the people in the study below was 12 weeks, but a subset of patients were treated for 8 weeks.

The SURVEYOR-I AND SURVEYOR-II phase 2 clinical trial results are listed in the table below from an ENANTA company press release.

Overview of SURVEYOR-I and SURVEYOR-II Clinical Data Presented at AASLD:

Phase 3 Clinical Trials:

Four studies of AbbVie’s two drug combination—glecaprevir (protease inhibitor) and pibrentasvir (NS5A inhibitor) were presented.

Endurance 1:703 genotype 1 non-cirrhotic treatment naïve and treatment experience patients. The patients were treated for 8 or 12 weeks. No ribavirin was used in the study. The cure rates were 99% to 100% across all treatment groups. Endurance 2: 199 genotype 2 non-cirrhotic treatment-naïve and treatment-experience patients treated for 12 weeks achieved 99% to 100%.

Surveyor-II Part 3 Phase 2/3: In genotype 3 patients who were cirrhotic and treatment experienced but who had not been previously treated with a NS5A inhibitor were treated with glecaprevir plus pibrentasvir. Those treated for 12 weeks achieved 91% to 98% cure rates and those treated for 16 weeks achieved 96% cure rates. This treatment was particularly effective for people with end-stage kidney disease.

Surveyor-II Part 4: In genotype 2, 4, 5 or 6 patients without cirrhosis. There were a total of 203 patients—both treatment naïve and treatment experienced (no NS5A treatment experienced). The treatment period was 8 weeks. The cure rates were 98% for genotype 2; 93% for genotype 4; 100% for genotype 5 and 90% for genotype 6—although the number of patients in the genotype 5 and 6 groups were very small.

Expedition-IV: The goal of the study was to treat patients with renal impairment. There were 104 genotype 1 through 6 patients enrolled. The majority of the patients had severe renal impairment, and 82% were on dialysis (filtering of the blood because the kidneys are impaired). The patients were treatment naïve and treatment experienced (no NS5A experienced). The cure rate was 99% (103 of 104)—one patient discontinued treatment before the trial ended.

AbbVie has submitted their study results to the Food and Drug Administration forapproval inDecember.

Alan Franciscus is the Executive Director of the Hepatitis C Support Project and Editor-in-Chief of the HCV Advocate.